| 1. |
- Ziegelasch, Hans-Juergen, et al.
(författare)
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Caring for diabetic patients in Germany - what is going wrong?
- 2022
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Ingår i: DIABETOLOGIE UND STOFFWECHSEL. - : GEORG THIEME VERLAG KG. - 1861-9002 .- 1861-9010. ; 17:5, s. 377-381
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Tidskriftsartikel (refereegranskat)abstract
- Germany has a good healthcare system. For diabetics there are in addition to family doctor medical care, diabetes specialist practices (DSP) and rehabilitation clinics. However, the care of diabetics in our country is not optimal. What are the causes and what can we do? Regional differences in the definition and demarcation of a DSP from other diagnoses, too few diabetologists and DSP, advertising for unhealthy food and insufficient self-monitoring are just a few of the causes. A registration of the diabetics in a national register similar to that in Sweden, a significant improvement of prophylaxis and the training of diabetology professionals are possible approaches for a positive change.
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| 2. |
- Eloff, Emma, et al.
(författare)
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Autoantibodies are major predictors of arthritis development in patients with anti-citrullinated protein antibodies and musculoskeletal pain
- 2021
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Ingår i: Scandinavian Journal of Rheumatology. - : Taylor & Francis Group. - 0300-9742 .- 1502-7732. ; 50:3, s. 189-197
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Predictors of arthritis development are highly warranted among patients with anti-citrullinated protein antibodies (ACPAs) and musculoskeletal symptoms to optimize clinical management. We aimed to identify clinical and laboratory predictors of arthritis development, including biochemically assessed alcohol consumption, among ACPA-positive patients with musculoskeletal pain.Method: 82 ACPA-positive individuals with musculoskeletal pain but no clinical arthritis were followed for a median of 72 months (interquartile range 57–81 months). We evaluated the prognostic value of baseline clinical and laboratory factors including smoking, symptom duration, age, gender, shared epitope, rheumatoid factor (RF), anti-carbamylated protein antibodies, ACPA levels, erythrocyte sedimentation rate, C-reactive protein levels, tender joint count, patient-reported general well-being, 28-joint Disease Activity Score, and alcohol consumption as measured by phosphatidyl ethanol (PEth) levels in whole blood.Results: During follow-up, 48% developed at least one arthritis. Multivariable analysis revealed an increased risk of arthritis development with RF positivity [hazard ratio (HR) = 2.3, 95% confidence interval (CI) 1.1–4.8, p = 0.028] and higher ACPA levels (HR = 1.0, 95% CI 1.000–1.001, p = 0.002). High levels of RF (HR = 4.4, 95% CI 1.7–11) entailed the highest HR in this ACPA-positive population. Neither clinical characteristics nor alcohol consumption measured by PEth conferred significant prognostic value.Conclusions: ACPA levels and concurrent presence of RF are independent predictors of arthritis development among ACPA-positive patients with musculoskeletal pain. The results are compatible with a dose–response relationship between RA-related autoantibodies and risk of arthritis development.
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| 3. |
- Enocsson, Helena, et al.
(författare)
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Serum levels of the soluble urokinase plasminogen activator receptor (suPAR) correlates with disease activity in early rheumatoid arthritis and reflects joint damage over time
- 2021
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Ingår i: Translational Research. - : Elsevier Science INC. - 1931-5244 .- 1878-1810. ; 232, s. 142-149
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Tidskriftsartikel (refereegranskat)abstract
- Soluble urokinase plasminogen activator receptor (suPAR) is intensively studied as a biomarker of inflammation and disease outcome in various diseases. In rheumatoid arthritis (RA), suPAR have shown an association with inflammation and swollen joints, but data on suPAR in relation to early disease course and disease progression are lacking. This study investigates the potential of suPAR to predict or reflect disease outcome in early RA. Serum suPAR was measured by enzyme-linked immunosorbent assay at disease onset and after 3 and 36 months in 252 patients from a Swedish prospective observational early RA cohort. Levels and changes of suPAR were analyzed in relation to the 28-joint disease activity score (DAS28) and joint damage according to the Larsen score at inclusion and during follow-up. 100 healthy blood donors served as controls. Circulating levels of suPAR were higher in RA patients at all time points as compared to healthy controls. Baseline suPAR was significantly associated with baseline disease activity whereas suPAR levels at 36 months were associated with joint damage at 36 months. No predictive value of suPAR levels or changes in suPAR levels over time were found. In conclusion, suPAR levels associate with disease activity in early untreated RA and reflects joint damage at later stages. Increased suPAR in established RA could indicate patients in need of frequent monitoring of joint status, irrespective of disease activity. In the view of suPAR as a rapidly emerging biomarker, it is important to be aware of its ability to reflect both inflammation and subsequent damage. (Translational Research 2021; 232:142-149)
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| 4. |
- Hammer, Hilde Berner, et al.
(författare)
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Rheumatoid arthritis patients with predominantly tender joints rarely achieve clinical remission despite being in ultrasound remission
- 2021
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Ingår i: Rheumatology. - : Oxford University Press. - 2514-1775. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Given that subjective variables might reduce remission by composite DAS (CDAS), the main objectives were to explore whether RA patients with mainly tender vs mainly swollen joints had differences in patient-reported outcome measures (PROMs), clinical or US assessments or in achieving remission defined by CDAS or US. Methods. In a Nordic multicentre study, RA patients initiating tocilizumab were assessed by PROMs, clinical, laboratory and US assessments (36 joints and 4 tendons) at baseline, 4, 12 and 24 weeks. Remission was defined according to clinical disease activity index (CDAI)/Boolean or no Doppler activity present. Tender-swollen joint differences (TSJDs) were calculated. Statistics exploring changes over time/differences between groups included Wilcoxon, Mann-Whitney, Kruskal-Wallis and Spearman tests. Results. One hundred and ten patients were included [mean (S.D.) age 55.6 (12.1) years, RA duration 8.7 (9.5) years]. All PROMs, clinical, laboratory and US scores decreased during follow-up (P < 0.001). During follow-up, tender joint counts were correlated primarily with PROMs [r = 0.24-0.56 (P < 0.05-0.001)] and swollen joint counts with US synovitis scores [r = 0.33-0.72 (P < 0.05-0.001)]. At 24 weeks, patients with TSJD > 0 had higher PROMs and CDAI (P < 0.05-0.001) but lower US synovitis scores (P < 0.05). Remission by CDAI/Boolean was seen in 26-34% and by Doppler 53%, but only 2-3% of patients with TSJD > 0 achieved CDAI/Boolean remission. Conclusion. Patients with more tender than swollen joints scored higher on subjective assessments but had less US synovitis. They seldom achieved CDAS remission despite many being in Doppler remission. If patients with predominantly tender joints do not reach CDAS remission, objective assessments of inflammation should be performed.
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| 5. |
- Kastbom, Alf, et al.
(författare)
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Changes in anti-citrullinated protein antibody isotype levels in relation to disease activity and response to treatment in early rheumatoid arthritis
- 2018
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Ingår i: Clinical and Experimental Immunology. - : Wiley-Blackwell Publishing Inc.. - 0009-9104 .- 1365-2249. ; 194:3, s. 391-399
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is a chronic inflammatory disease where serum analysis of anti-citrullinated peptide/protein antibodies (ACPA) is an important diagnostic/prognostic tool. Levels and changes of ACPA in RA patients have been studied previously in relation to disease course and therapy response, but less is known regarding ACPA isotype changes in early RA. Hence, recent-onset RA patients (n = 231) were subjected to a 3-year clinical and radiological follow-up. Serum samples were serially collected and ACPA isotypes were analysed using the second-generation cyclic citrullinated peptide (CCP) as capture antigen. Changes in ACPA isotype levels and status were related to disease course and pharmacotherapy. At inclusion, 74% of the patients tested positive for ACPA IgG; 55% for immunoglobulin (Ig)A, 37% for secretory IgA (SIgA) and 35% for IgM. The proportion of positive patients decreased significantly at follow-up regarding ACPA SIgA, IgM and IgA. During the initial 3 months, reduction of the 28-joint disease activity score (DAS28) correlated with reduced levels of ACPA IgG (Rho = 0 center dot 242, P = 0 center dot 003), IgA (Rho = 0 center dot 260, P = 0 center dot 008), IgM (Rho = 0 center dot 457, P amp;lt; 0 center dot 001) and SIgA (Rho = 0 center dot 402, P amp;lt; 0 center dot 001). Levels of ACPA SIgA (P = 0 center dot 008) and IgM (P = 0 center dot 021) decreased significantly among patients with good response to treatment, which was not seen regarding ACPA IgA or IgG. Changes in ACPA isotype levels were not associated with radiographic damage. In conclusion, ACPA SIgA and IgM declined rapidly upon anti-rheumatic therapy and correlated with decreased disease activity in recent-onset RA. This may indicate that down-regulation of mucosal immunity to citrullinated proteins/peptides and recruitment of new B cells are key features of therapy responses in early RA.
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| 6. |
- Martinsson, Klara, et al.
(författare)
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Elevated free secretory component in early rheumatoid arthritis and prior to arthritis development in patients at increased risk
- 2020
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 59:5, s. 979-987
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Considering growing evidence of mucosal involvement in RA induction, this study investigated circulating free secretory component (SC) in patients with either recent-onset RA or with ACPA and musculoskeletal pain. Methods. Two prospective cohorts were studied: TIRA-2 comprising 452 recent-onset RA patients with 3 years of clinical and radiological follow-up, and TIRx patients (n = 104) with ACPA IgG and musculoskeletal pain followed for 290 weeks (median). Blood donors and three different chronic inflammatory diseases served as controls. Free SC was analysed by sandwich ELISA. Results. Serum levels of free SC were significantly higher in TIRA-2 patients compared with TIRx and all control groups (P < 0.01). Among TIRx patients who subsequently developed arthritis, free SC levels were higher compared with all control groups (P < 0.05) except ankylosing spondylitis (P = 0.74). In TIRA-2, patients with ACPA had higher baseline levels of free SC compared with ACPA negative patients (P < 0.001). Free SC status at baseline did not predict radiographic joint damage or disease activity over time. In TIRx, elevated free SC at baseline trendwise associated with arthritis development during follow-up (P = 0.066) but this disappeared when adjusting for confounders (P = 0.72). Cigarette smoking was associated with higher levels of free SC in both cohorts. Conclusion. Serum free SC levels are increased in recent-onset RA compared with other inflammatory diseases, and associate with ACPA and smoking. Free SC is elevated before arthritis development among ACPA positive patients with musculoskeletal pain, but does not predict arthritis development. These findings support mucosal engagement in RA development.
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| 7. |
- Roos, Karin, et al.
(författare)
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Circulating secretory IgA antibodies against cyclic citrullinated peptides in early rheumatoid arthritis associate with inflammatory activity and smoking
- 2016
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Ingår i: Arthritis Research & Therapy. - : BIOMED CENTRAL LTD. - 1478-6362. ; 18:119
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Tidskriftsartikel (refereegranskat)abstract
- Background: A possible association between mucosal immunization and inflammation, as well as the initiation and propagation of rheumatoid arthritis (RA), is attracting renewed interest. The aim of this study was to evaluate the possible occurrence and clinical correlations of circulating secretory immunoglobulin A (SIgA) antibodies against the second-generation cyclic citrullinated peptides (CCP) among patients with recent-onset RA followed prospectively over 3 years. Methods: Baseline serum samples from 636 patients with recent-onset RA were analyzed for SIgA anti-CCP antibodies by using an enzyme-linked immunosorbent assay with a secondary antibody directed against secretory component. SIgA anti-CCP status at baseline was analyzed in relation to smoking, HLA-DRB1/shared epitope (SE), and the disease course over 3 years. Significant findings were evaluated in regression analysis that included age, sex, smoking, and SE. Results: Seventeen percent of the patients tested positive for circulating SIgA anti-CCP, and the occurrence was confirmed by detection of secretory component in an affinity-purified IgA anti-CCP fraction. SIgA anti-CCP positivity at baseline was associated with slightly higher baseline erythrocyte sedimentation rate (ESR) (mean 38 vs. 31 mm/first hour, p = 0.004) and C-reactive protein (CRP) (mean 30 vs. 23 mg/L, p = 0.047). During follow-up, SIgA anti-CCP-positive patients had a higher mean AUC regarding ESR (adjusted p = 0.003), although there were no significant differences regarding CRP, tender and swollen joint counts, or radiological joint damage (median Larsen progression 1.0 vs. 1.0, p = 0.22). SIgA anti-CCP was associated significantly with smoking (79 % ever smokers among SIgA anti-CCP-positive patients vs. 59 % in SIgA anti-CCP-negative patients, adjusted OR 2.19, 95 % CI 1.01-4.37, p = 0.027) but not with carriage of the SE (80 % vs. 73 %, p = 0.62). Conclusions: Circulating SIgA anti-CCP, which is present in a subgroup of patients with early RA, is not related to SE, but it is environmentally linked to cigarette smoking. This finding strengthens the hypothesis that immunization against citrullinated peptides and/or proteins may occur at mucosal surfaces of the airways. Analysis of SIgA antibodies in serum may be a convenient and more versatile means to investigate the "mucosal connection" in RA compared with analyses in mucosal fluid samples.
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| 8. |
- Ziegelasch, Michael, et al.
(författare)
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Anti-cyclic citrullinated peptide antibodies are associated with radiographic damage but not disease activity in early rheumatoid arthritis diagnosed in 2006-2011
- 2020
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Ingår i: Scandinavian Journal of Rheumatology. - : Taylor & Francis. - 0300-9742 .- 1502-7732. ; 49:6, s. 434-442
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The discovery of anti-citrullinated protein antibodies (ACPAs) and the introduction of new therapeutic options have had profound impacts on early rheumatoid arthritis (RA) care. Since ACPA status, most widely assessed as reactivity to cyclic citrullinated peptides (CCPs), influences treatment decisions in early RA, we aimed to determine whether anti-CCP remains a predictor of disease activity and radiographic joint damage in more recent 'real-world' early RA.Method: Two observational early RA cohorts from Sweden enrolled patients in 1996-1999 (TIRA-1, n = 239) and 2006-2009 (TIRA-2, n = 444). Clinical and radiographic data and ongoing treatment were prospectively collected up to 3 years. Two other cohorts served as confirmation cohorts (TRAM-1, with enrolment 1996-2000, n = 249; and TRAM-2, 2006-2011, n = 528). Baseline anti-CCP status was related to disease activity, pharmacotherapy, and radiographic joint damage according to Larsen score.Results: In the TIRA-1 cohort, anti-CCP-positive patients had significantly higher 28-joint Disease Activity Score, swollen joint count, C-reactive protein level, and erythrocyte sedimentation rate during follow-up compared with anti-CCP-negative patients. In TIRA-2, no such differences were found, but baseline anti-CCP positivity was associated with higher 3 year Larsen score (5.4 vs 3.5, p = 0.039). In TRAM-2, anti-CCP also predicted radiographic damage (8.9 vs 6.7, p = 0.027), with no significant differences in disease activity.Conclusion: In the early RA cohorts recruiting patients in 2006-2011, baseline anti-CCP positivity was not associated with disease activity over time, but was associated with increased radiographic damage at follow-up. Hence, close radiographic monitoring is warranted in early anti-CCP-positive RA regardless of disease activity.
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| 9. |
- Ziegelasch, Michael, et al.
(författare)
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Antibodies against carbamylated proteins and cyclic citrullinated peptides in systemic lupus erythematosus : results from two well-defined European cohorts.
- 2016
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Ingår i: Arthritis Research & Therapy. - : BioMed Central. - 1478-6362. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Articular manifestations are common in systemic lupus erythematosus (SLE) whereas erosive disease is not. Antibodies to cyclic citrullinated peptide (anti-CCP) are citrulline-dependent in rheumatoid arthritis (RA), whereas the opposite is suggested in SLE, as reactivity with cyclic arginine peptide (CAP) is typically present. Antibodies targeting carbamylated proteins (anti-CarP) may occur in anti-CCP/rheumatoid factor (RF)-negative cases long before clinical onset of RA. We analysed these antibody specificities in sera from European patients with SLE in relation to phenotypes, smoking habits and imaging data.METHODS: Cases of SLE (n = 441) from Linköping, Sweden, and Leiden, the Netherlands, were classified according to American College of Rheumatology (ACR) and/or Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria. IgG anti-CCP, anti-CAP and anti-CarP were analysed by immunoassays. Radiographic data from 102 Swedish patients were available.RESULTS: There were 16 Linköping (6.8%) and 11 Leiden patients (5.4%) who were anti-CCP-positive, of whom approximately one third were citrulline-dependent: 40/441 (9.1%) were anti-CarP-positive, and 33% of the anti-CarP-positive patients were identified as anti-CCP-positive. No associations were found comparing anti-CCP or anti-CarP with ACR-defined phenotypes, immunologic abnormalities or smoking habits. Radiographically confirmed erosions were found in 10 patients, and were significantly associated with anti-CCP, anti-CarP and RF. Musculoskeletal ultrasonography scores were higher in anti-CCP-positive compared to anti-CCP-negative patients.CONCLUSIONS: In the hitherto largest anti-CarP study in SLE, we demonstrate that anti-CarP is more prevalent than anti-CCP and that the overlap is limited. We obtained some evidence that both autoantibodies seem to be associated with erosivity. Similar pathogenetic mechanisms to those seen in RA may be relevant in a subgroup of SLE cases with a phenotype dominated by arthritis.
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| 10. |
- Ziegelasch, Michael, et al.
(författare)
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Bone Erosions Detected by Ultrasound Are Prognostic for Clinical Arthritis Development in Patients With ACPA and Musculoskeletal Pain
- 2021
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Ingår i: Frontiers in Medicine. - : FRONTIERS MEDIA SA. - 2296-858X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Anti-citrullinated protein antibodies (ACPA) often precede onset of rheumatoid arthritis (RA) by years, and there is an urgent clinical need for predictors of arthritis development among such at-risk patients. This study assesses the prognostic value of ultrasound for arthritis development among ACPA-positive patients with musculoskeletal pain. We prospectively followed 82 ACPA-positive patients without clinical signs of arthritis at baseline. Ultrasound at baseline assessed synovial hypertrophy, inflammatory activity by power Doppler, and erosions in small joints of hands and feet. We applied Cox regression analyses to examine associations with clinical arthritis development during follow-up (median, 69 months; range, 24-90 months). We also compared the ultrasound findings among the patients to a control group of 100 blood donors without musculoskeletal pain. Clinical arthritis developed in 39/82 patients (48%) after a median of 6 months (range, 1-71 months). One or more ultrasound erosions occurred in 13/82 patients (16%), with none in control subjects (p < 0.001). Clinical arthritis development was more common among patients with baseline ultrasound erosions than those without (77 vs. 42%, p = 0.032), and remained significant in a multivariable Cox regression analysis that included previously described prognostic factors (HR 3.9, 95% CI 1.6-9.4, p = 0.003). Ultrasound-detected tenosynovitis was more frequent among the patients and associated with clinical arthritis development in a univariable analysis (HR 2.5, 95% CI 1.1-5.7, p = 0.031), but did not remain statistically significant in multivariable analysis. Thus, bone erosions detected by ultrasound are independent predictors of clinical arthritis development in an ACPA-positive at-risk population.
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